05-01-2019 What is Epidiolex®?

Toxicology Question of the Week

May 1, 2019

What is Epidiolex®?

Epidiolex is the first FDA approved medication consisting of highly purified, plant based, pharmaceutical grade cannabidiol (CBD) extract.

f1                 Figure 1: Epidiolex®          f2     Figure 2: Cannabidiol chemical structure

Cannabidiol, CBD, is a cannabinoid that naturally occurs in the Cannabis sativa plant. Cannabis has been used for over 4,000 years with varied success to treat ailments including chronic pain, eating disorders, rheumatism, and convulsions. In the 19th century, neurologists noted the potential effectiveness of cannabis for treating seizure disorders. Research since has continued to evaluate cannabis as a treatment option for epilepsy. Cannabis sativa contains several active compounds, of which tetrahydrocannabidiol (THC) and cannabidiol (CBD) are the most well-studied. THC, a psychoactive agent, has both anticonvulsant and proconvulsant properties, while CBD, with no notable psychoactive effects, is consistently an anticonvulsant.

The mechanism of action by which CBD exerts its anti-seizure effect is yet to be fully elucidated. Emerging studies suggest that the anticonvulsant properties of CBD may be unrelated to its activity at the cannabinoid receptor but may stem from modulation of ion channels, transporters, enzymes, and receptors. Recent work suggests that CBD may inhibit voltage-gated sodium channels, though differential effects on excitatory versus inhibitory neurons are unknown.

On June 25, 2018, the FDA approved Epidiolex® (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. Subsequently, on September 27, 2018, the U.S. Department of Justice and Drug Enforcement Administration placed Epidiolex in Schedule V.

The most common adverse reactions in patients receiving Epidiolex® (≥10% and greater than placebo) include somnolence; decreased appetite; diarrhea; transaminase elevations; fatigue, malaise, and asthenia; rash; insomnia, sleep disorder and poor-quality sleep; and infections. Hematologic abnormalities were also observed.

Moderate or strong inhibitors or inducers of CYP3A4 and CYP2C19 may affect Epidiolex® exposure. Epidiolex® may affect exposure to CYP2C19 substrates (e.g., clobazam, diazepam) or others. Concomitant use of Epidiolex® and valproate increases the incidence of liver enzyme elevations. Dosage adjustment of Epidiolex® or other concomitant medications may be necessary.

If you have questions or concerns about CBD exposure, the poison center has certified specialists in poison information waiting 24/7 to assist you. Please, don’t hesitate to call 1-800-222-1222.

This question was prepared by: Jeff Moore, BS, RN, CSPI

REFERENCES:

  1. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.
  2. FDA News Release. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. 2018. Accessed October 11, 2018.
  3. Pickrell WO, Robertson NP. Cannabidiol as a treatment for epilepsy. J Neurol. 2017;264(12):2506-2508.
  4. Sanmartin PE, Detyniecki K. Cannabidiol for epilepsy: new hope on the horizon? Clin Ther. 2018;40(9): 1438-1441.
  5. Berkovic SF. Cannabinoids for epilepsy—real data, at last. N Engl J Med. 2017;376(21):2075-2076.
  6. Ghovanloo M-R, Shuart NG, Mezeyova J, et al. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J Biol Chem. 2018;293(43):16546-16558.
  7. FDA-approved drug Epidiolex placed in schedule V of Controlled Substance Act. www.dea.gov/press-releases/ 2018/09/27/fda-approved-drug-epidiolex-placed-schedule-v-controlled-substance-act. 2018. Accessed October 11, 2018.
  8. EPIDIOLEX, Product Fact Sheet, Greenwich Biosciences, Inc., Carlsbad, CA 92008

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vumc.org.

Donna Seger, MD

Executive Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222